A. Regulation of C3 and C5 gene expression: The controlled regulation of C3 and/or C5 gene expression - ideally from the cell surface - would be an additional means to manipulate Th1 and CTL responses at will. In collaboration with Steve Holland (NIAID, NIH) and Adrian Hayday (KCL), we have identified the integrin LFA-1 as a master regulator of C3 gene expression in a range of immune cells and are currently assessing the in vivo significance and druggability of this novel integrin/complement cross-talk. A manuscript will be submitted by the end of October 2018. B. Direct regulation of IL-10 production: We have identified a receptor that, when activated, completely abrogates IL-10 switching in Th1 cells. We are currently assessing the signaling pathway driven by this receptor that leads to the loss of IL-10 production in CD4+ T cells. We have additionally identified a novel role for fatty acid metabolism as driver of human CTL full killing capacity and the work is in press in Nature Communications.
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